The estrogenic hormones act via a specific estrogen receptor to exert profound effects upon uterine growth and development. We propose to investigate the molecular mechanism of estrogen action at the receptor level. The estrogen-binding and molecular properties of the receptor from the rat, calf and human uterus will be characterized. The estrogen and temperature-mediated activation of the estrogen receptor will be measured by the receptor's estrogen-binding kinetics. The structural changes of the estrogen receptor induced by the activation process will be defined. The receptor will be purified and its molecular properties measured. The interactions of the nonactivated and activated estrogen receptors with nuclei, chromatin, and PNA will be investigated. Ultimately, this system when reconstructed from the purified components will be useful in understanding the interactions of the receptor will the uterine nuclei, the receptor's control of RNA synthesis, and will thereby provide knowledge of the mechanism of estrogen regulation of normal and abnormal uterine growth.